A Novel Diagnostic Biomarker Panel for Obesity-related Nonalcoholic Steatohepatitis (NASH)

Younossi, Zobair M.; Jarrar, Mohammed; Nugent, Clare; Randhawa, Manpreet; Afendy, Mariam; Stepanova, Maria; Rafiq, Nila; Goodman, Zachary; Chandhoke, Vikas; Baranova, Ancha

doi:10.1007/s11695-008-9506-y

Cited by 246 publications

(211 citation statements)

References 31 publications

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“…Methods such as ranked assessment (classifying as better, worse, or unchanged), or a truly quantitative measurement of the area of fibrosis by micromorphometry could be useful especially in early phase trials. Importantly, biomarkers for each cardinal feature of steatohepatitis [56][57][58][59][60][61][62] need to be developed and validated for longitudinal changes on therapy.…”

Section: Lessons For the Design Of Future Clinical Trialsmentioning

confidence: 99%

Therapeutic trials in nonalcoholic steatohepatitis: Insulin sensitizers and related methodological issues

2010

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Insulin sensitizers are attractive candidate therapies for nonalcoholic steatohepatitis mainly because of the strong association between this disease and insulin resistance. This review provides a critical overview of the mechanisms of action, clinical trial results, and safety issues of metformin and glitazones in nonalcoholic steatohepatitis. It also highlights methodological challenges for trial design and proposes endpoints for future proof of principle, registrational, and postmarketing trials. (HEPATOLOGY 2010;52:2206-2215 N onalcoholic steatohepatitis (NASH) is emerging as the next big therapeutic challenge in hepatology. 1 Currently the top cause of newly identified chronic liver diseases, NASH has potential for fibrosis, cirrhosis decompensation, and hepatocellular carcinoma. Not all individuals with metabolic risk factors will experience these adverse outcomes and identifying those at risk is critical. Prognostic markers for progression have mostly been derived from histological studies. Compared to steatosis alone or to steatosis and minimal inflammation, the coexistence of inflammation, cell injury (ballooning), and steatosis, a pathological aggregate labeled steatohepatitis, is associated with a significant increase in overall mortality and in liver-related mortality. The degree of inflammation is the best predictor of fibrosis progression, 2 a widely accepted surrogate for hard endpoints such as cirrhosis, endstage liver disease, and possibly hepatocellular carcinoma.Insulin resistance (IR) is consistently found in patients with NASH in both cross-sectional and longitudinal studies. Moreover, there is a stepwise increase in the severity of IR and its phenotypic complications (clustered as elements of the metabolic syndrome) between normal liver, isolated steatosis, and steatohepatitis that has prompted speculation that IR might contribute to liver damage. Logically, most therapeutic trials focused on insulin sensitizers (IS) as candidate therapies.The aim of this report is to critically review the results of trials of metformin and glitazones for NASH. We highlight methodological challenges for trial design and propose endpoints for future proof of principle, registrational, and postmarketing trials.

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Section: Lessons For the Design Of Future Clinical Trialsmentioning

confidence: 99%

Therapeutic trials in nonalcoholic steatohepatitis: Insulin sensitizers and related methodological issues

2010

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“…Reactive oxygen species: cytochrome P-450, 111 myeloperoxidase, nitric oxide synthase, lipid peroxidation products such as oxidized LDL, thiobarbituric acid-reacting substances 112 2. Inflammatory: TNFa, 113 adiponectine, 57,58,114,115 CRP, 48,83 visfatin, resistin, interleukin-6 and retinol binding protein-4 75,82 3. Apopetosis: cytokine-18 51,52 and fibrosis: hyaluronic acid 114 Table 2 represents the research results about the role of this group in predicting NASH.…”

Section: Biomarkersmentioning

confidence: 99%

“…111 Increased expression of proinflammatory cytokines such as TNFa and interleukin1b was may be responsible for observed decreases in respective P-450 activity. [113][114][115][116][117] Original European Liver Fibrosis study used age, tissue inhibitor of matrix metalloproteinase 1, hyaluronic acid, amino-terminal peptide of procollagen III for detection of fibrosis in fatty liver. In contrast, pathologists' agreement over histological scores ranged from very good to moderate (k ¼ 0.97-0.46).…”

Section: Biomarkersmentioning

confidence: 99%

Nonalcoholic fatty liver disease: a challenge for pediatricians

Widhalm

Ghods

2010

Int J Obes

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Background: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of pediatric liver disease. Its prevalence is related to the growing epidemic in childhood obesity during the past decades. At present, NAFLD and nonalcoholic steatohepatitis (NASH) are increasingly recognized worldwide. In spite of alarming trend in the epidemiology in pediatric field and growing risk of end stage liver disease, there is no significant advance in its diagnosis and treatment. Aim: To provide a detailed review for diagnosis and management of NAFLD and NASH. Methods: By using Pubmed to find review articles and relevant research. Results: The prevalence ranges from at least 3% in children overall to about 50% in obese children. The noninvasive biomarkers can be used to identify NAFLD/NASH patients. Diagnostic criteria based on biochemical and immunological indicators in the high-risk group of children could prevent about half of cases from receiving an invasive test. The pharmacological and surgical interventions have shown a growing role in pediatric NAFLD. Novel treatment modalities, such as probiotics, have hardly been studied. Conclusion: Early diagnosis by using noninvasive screening methods in high-risk groups is the most effective strategy against the NAFLD. The biology of early growth and development, including hepatic metabolism, may hold the key to pediatric NAFLD. Prevention of overweight children and childhood obesity is undoubtedly the best strategy for treating NAFLD.

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“…Adiponectin, TNF-a and leptin were not associated with the extent of hepatic fibrosis Bugianesi et al (24) 174 NAFLD patients and 42 controls Adiponectin serum levels were inversely correlated to the percentage of hepatic fat content and no association was established with necroinflammation or fibrosis Pagano et al (18) 17 NAFLD patients and 20 matched controls Plasma adiponectin was significantly lower in NAFLD patients than controls but similar in simple steatosis and in steatohepatitis Targher et al (19) 60 NAFLD patients and 60 controls. Low adiponectin levels independently predicted hepatic steatosis and necroinflammation but not fibrosis Wong et al (21) 80 NAFLD patients and 41 healthy controls Low adiponectin level and increased leptin level were associated with NAFLD.…”

mentioning

confidence: 99%

“…After performing this review, one can conclude that the information available on this particular topic is still controversial and that the role of determining the levels of one or two adipokines to reliably exclude the aggressive forms of the disease in NAFLD patients remains unclear. In contrast, the use of combined sets of clinical variables and serum determinations can augment the diagnostic performance across different stages of fibrosis and is promising (24). However, these panels must be validated in large and well-selected groups of NAFLD patients and carefully matched healthy controls before being accepted in daily clinical practice.…”

mentioning

confidence: 99%

The value of serum adipokine measurement in non‐alcoholic fatty liver disease

Arrese

Riquelme

2009

Liver International

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A Novel Diagnostic Biomarker Panel for Obesity-related Nonalcoholic Steatohepatitis (NASH)

Abstract: Four ELISA-based tests were combined to form a simple diagnostic biomarker for NASH.

Cited by 246 publications

References 31 publications

Therapeutic trials in nonalcoholic steatohepatitis: Insulin sensitizers and related methodological issues

Therapeutic trials in nonalcoholic steatohepatitis: Insulin sensitizers and related methodological issues

Nonalcoholic fatty liver disease: a challenge for pediatricians

The value of serum adipokine measurement in non‐alcoholic fatty liver disease

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